We propose to study the products and mechanism of reaction of glucose-6-phosphate and glucose (found in red cells in elevated concentrations in diabetes), and 5-deoxy-xylulose-1-phosphate (found in red cells in elevated concentrations in alcoholism) with hemoglobin by P-31 and C-13 NMR, column chromatography, isoelectric focusing, and isopycnic centrifugation. The unique properties of P-31 and C-13 NME will allow us to study unfractionated mixtures and intact cells as well as solutions. This is particularly important for the study of sugars and phosphorylated compounds since both are notorious for decomposing of re-arranging. Us eof isopycnic centrifugation will allow us to resolve heterogeneous cell populations which may otherwise obscure important effects. These observations should extend our understanding of the mechanism of specific tissue damage in diabetics and possibly alcoholics as well. The effect of glycosylation and reaction with xyulose-1-phosphate on the hemoglobins and red cells of individuals with hemoglobinopathies such as sickle cell disease and thalassemia will be investigated.